The purpose of this randomized, two-arm, open-label expansion phase study is to collect preliminary efficacy data of panobinostat at the recommended phase II dose (RPIID) level in combination with azacytidine (5-Aza) versus an active control arm 5-Aza alone. This randomized phase II part allows also collecting safety data of panobinostat in combination with 5-Aza in comparison to single-agent 5-aza.

Each dose of panobinostat should be taken with 240 mL of water. Patients should be instructed to swallow the capsules whole and not chew them.

If the patient forgets to take his/her dose during the morning on a scheduled treatment day then the missed dose should be taken on that same day within 12 hours. After more than 12 hours, that day's dose should be withheld, and the patient should wait to take panobinostat until the next scheduled treatment day. The patient should then continue treatment with the original dosing schedule.

The days when panobinostat and 5-Aza are scheduled together (Day 3 and Day 5 of a treatment cycle), panobinostat should be administered approximately 30 min prior to 5-Aza.

Drug: 5-Azacytidine

Study Arm (s)

Experimental: Panobinostat + 5-Azacytidine

In phase I: Panobinostat : Escalating doses starting with 20 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15.

In phase II: Panobinostat : Rapid Phase II doses at 30 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15.

In both phases, dose of 5-Azacytidine will be 75 mg/m^2, subcutaneously Daily for Day 1 to Day 7.

Intervention: Drug: Panobinostat (LBH589) and 5-Azacytidine

Active Comparator: 5-Azacytidine

Dose of 5-Azacytidine : 75 mg/m^2 subcutaneously daily from Day 1 to Day 7.

Intervention: Drug: 5-Azacytidine

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Active, not recruiting

Enrollment ICMJE

112

Estimated Completion Date

June 2015

Estimated Primary Completion Date

June 2015 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Phase l:

Patients with cytopathologically confirmed diagnosis of AML according to WHO criteria, excluding acute promyelocytic leukemia who are eligible for Vidaza treatment

ECOG performance status greater less than or equal to 2

Phase ll:

Adult patients (age ≥ 18 years) who are candidates for treatment with 5-Aza and present with one of the following:

intermediate-2 or high-risk myelodysplastic syndromes according to the International Prognostic Scoring System (IPSS). OR

AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR